title: Sevoflurane preconditioning induces neuroprotection through reactive oxygen species-mediated up-regulation of antioxidant enzymes in rats.
abstract: BACKGROUND
  It has been reported that sevoflurane preconditioning can induce neuroprotection, the mechanisms of which, however, are poorly elucidated. We designed the present study to examine the hypothesis that sevoflurane preconditioning could reduce cerebral ischemia- reperfusion injury through up-regulating antioxidant enzyme activities before ischemic injury by generating reactive oxygen species (ROS).
  
  
  METHODS
  In preconditioning groups, adult male Sprague-Dawley rats were pretreated with 1 hour sevoflurane exposure at a dose of 1%, 2%, or 4% for 5 consecutive days. At 24 hours after the last exposure, all rats were subjected to focal brain ischemia induced by middle cerebral artery occlusion for 120 minutes followed by 72-hour reperfusion. The role of ROS in ischemic tolerance was assessed by administration of the free radical scavenger dimethylthiourea and antioxidant N-acetylcysteine before each preconditioning. Brain ischemic injury was evaluated by neurologic behavior scores and brain infarct volume calculation. Antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase [GSH-px]) of brain tissue and blood serum were tested at 24 hours after the last sevoflurane preconditioning.
  
  
  RESULTS
  Sevoflurane preconditioning reduced infarct size and improved neurobehavioral outcome in a dose-dependent manner. The neuroprotective effects of sevoflurane preconditioning were abolished by dimethylthiourea and N-acetylcysteine. The activities of catalase and glutathione peroxidase (GSH-px) in the brain tissue were elevated by sevoflurane preconditioning before ischemic injury. The up-regulated activity of GSH-px in serum negatively correlated with brain infarct volume percentage.
  
  
  CONCLUSIONS
  Sevoflurane preconditioning induces cerebral ischemic tolerance in a dose- response manner through ROS release and consequent up-regulation of antioxidant enzyme activity before ischemic injury in rats. Serum GSH-px activity could be developed as a marker to assess the effectiveness of sevoflurane preconditioning before ischemia.
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
authors.forename: Qianzi
authors.initials: Q
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.forename: Jiao
authors.initials: J
authors.lastname: Deng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Ruidong
authors.initials: R
authors.lastname: Ye
authors.forename: Xuying
authors.initials: X
authors.lastname: Li
authors.forename: Sheng
authors.initials: S
authors.lastname: Hu
authors.forename: Hailong
authors.initials: H
authors.lastname: Dong
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002545:Brain Ischemia / Q000201:enzymology* / Q000517:prevention & control; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077149:Sevoflurane; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000975:Antioxidants; D008738:Methyl Ethers; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D000077149:Sevoflurane